Muscarinic cholinergic receptors mediate many of the actions of the neurotransmitter acetylcholine in the central and peripheral nervous systems, gastrointestinal system, heart, endocrine glands, lungs, and other tissues. Muscarinic receptors play a central role in the central nervous system for higher cognitive functions, as well as in the peripheral parasympathetic nervous system. Five distinct muscarinic receptor subtypes, referred to as subtypes M1-M5, have been identified. The M1 subtype is the predominant subtype found in the cerebral cortex in hippocampus and is believed to be involved in the control of cognitive functions; the M2 subtype is the predominant subtype found in heart and is believed to be involved in the control of heart rate; the M2 subtype is also found in brain regions such as cortex and hippocampus where it is predominantly located presynaptically; the M3 subtype is believed to be involved in gastrointestinal and urinary tract stimulation as well as sweating and salivation; the M4 subtype is present in the brain and may be involved in locomotion; the M5 receptor is present in the brain. M1 and M4 have been particularly associated with the dopaminergic system.
Pilocarpine is a pharmaceutical that has been used to treat glaucoma and to prevent other eye diseases and symptoms thereof. Pilocarpine is recognized as a non-selective muscarinic receptor agonist, and can cause unwanted side effects. Accordingly, there is a need for compounds, such as selective muscarinic agonists, that can increase acetylcholine signaling and/or effect in the brain via activity at specific muscarinic receptor subtypes in the central and peripheral nervous system, both as pharmacological tools and as therapeutic agents.